GABA sets the tempo for activity-dependent adult neurogenesis

Ge, Shaoyu; Pradhan, Dennis A.; Ming, Guo Li; Song, Hongjun

doi:10.1016/j.tins.2006.11.001

Cited by 328 publications

(296 citation statements)

References 68 publications

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“…In vitro application of NMDA on hippocampal precursor cells increased neuronal differentiation, whereas treatment with the antagonist APV decreased neuronal differentiation. At a later developmental stage, adult-born neurons express NMDARs (19,37) and functional glutamatergic afferents that have been described to occur in mice toward the end of the second week after birth (30,31). However, it has been recently shown that adult-born neuron maturation and functional recruitment into the dentate network is faster in rats compared with mice (38) and that glutamatergic afferents arrive earlier in rats, when newborn neurons are 10 days old (40), a time window consistent with our data.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, because GABAergic hilar interneurons are under glutamatergic control (41), a reduction in GABAergic signaling could be involved as well. Indeed, adult-born neurons first receive depolarizing GABA inputs that are known to promote the maturation of the new neurons (30,31,42,43). Further investigation is needed to elucidate the mechanisms through which glutamate regulates learning-induced changes in neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

Tronel

Fabre

Charrier

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

186

187

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Neurogenesis in the hippocampus is characterized by the birth of thousand of cells that generate neurons throughout life. The fate of these adult newborn neurons depends on life experiences. In particular, spatial learning promotes the survival and death of new neurons. Whether learning influences the development of the dendritic tree of the surviving neurons (a key parameter for synaptic integration and signal processing) is unknown. Here we show that learning accelerates the maturation of their dendritic trees and their integration into the hippocampal network. We demonstrate that these learning effects on dendritic arbors are homeostatically regulated, persist for several months, and are specific to neurons born during adulthood. Finally, we show that this dendritic shaping depends on the cognitive demand and relies on the activation of NMDA receptors. In the search for the structural changes underlying long-term memory, these findings lead to the conclusion that shaping neo-networks is important in forming spatial memories.adult neurogenesis | memory | spatial learning | hippocampus | dendrite I n the search for the mechanisms underlying long-term memory formation, structural changes have been proposed to play a major role (1). Adult neurogenesis, a novel form of structural plasticity, occurs in the dentate gyrus (DG), a key structure in processing spatial relational memory (2). Adult neurogenesis in the DG is a complex, multistep process that starts with the proliferation of neural precursors residing in the dentate subgranular layer (2). At least 50% of the daughter cells die within a few days after their birth. The adult-born cells that survive this initial period of cell death differentiate mainly into granule neurons. These new mature neurons are synaptically integrated into the dentate network, where they receive functional inputs (3) and form functional synapses with their target cells (4).Adult-born neurons contribute to the formation of memories, particularly spatial memory as measured in the water maze (5, 6). Reciprocally, spatial learning has been shown to influence adult neurogenesis (7). We have shown that during spatial learning and similar to the selective stabilization process observed during brain development, neuronal networks are sculpted by a tightly regulated selection and suppression of different populations of newly born neurons (8). This homeostatic regulation of the numbers of newly born neurons is important for spatial memory, because its alteration leads to memory deficits (8, 9).One of the requirements for the new neurons to process information is the development of extensive dendritic arbors capable of receiving and integrating complex spatiotemporal patterns of synaptic inputs (4). Whether learning influences such a dendritic development is unknown. To address this issue, we used doublecortin (Dcx) and retroviral labeling to examine to what extent spatial learning in the water maze affects the dendritic morphology of adult-born neurons. Furthermore, we investigated whether the ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

Tronel

Fabre

Charrier

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

186

187

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“…Angiogenesis and the expression of pro-angiogenic factors appear to play an important role both in progenitor cell proliferation and survival as well as migration , Yang, et al, 2011. In addition, alteration in neurochemical signaling, such as GABAergic and glutamtergic transmission, and neuronal activity have been shown to modulate neurogenesis following brain injury (Deisseroth, et al, 2004, Ge, et al, 2007. Thus, it appears multiple mechanisms underlie the regulation of compensatory neurogenesis following brain injury; these will be summarized in the following section.…”

Section: Factors Modulating Compensatory Neurogenesismentioning

confidence: 99%

“…Increased levels of GABA in the dentate gyrus during the early post-seizure period may also positively regulate hippocampal neurogenesis, as studies show that GABA has crucial roles in regulating various steps of adult neurogenesis, including progenitor cell proliferation, migration and differentiation of neuroblasts, and synaptic integration of adult-born neurons (Ge, et al, 2007). Further, increased levels of neuropeptide Y (NPY) found typically after acute seizures may enhance the proliferation of neural progenitor cells in the dentate gyrus, as studies have shown that neural progenitor cells increase neurogenesis in the presence of NPY (Howell, et al, 2003, Howell, et al, 2005, Howell, et al, 2007, Rodrigo, et al, 2010.…”

Section: Potential Mechanisms Of Increased Hippocampal Neurogenesis Amentioning

confidence: 99%

Compensatory Neurogenesis in the Injured Adult Brain

Connor¹

2012

Brain Injury - Pathogenesis, Monitoring, Recovery and Management

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“…Similarly, GlyR function was shown to be crucially involved in interneuron diVerentiation in zebraWsh (McDearmid et al 2006). For GABA A receptors, GABAinduced excitation was shown to cause the expression of brain derived neurotrophic factor (Berninger et al 1995) and NeuroD (Ge et al 2007), however, much less is known about GlyR regulated gene and protein expression proWles. Interestingly, it was demonstrated recently, that the neonatal GlyR 2 subunit may bind diVerent cellular signaling molecules like eEF1A, p70S6 kinase and calcineurin (Bluem et al 2007), supporting the hypothesis that also the GlyR might be important for the speciWc regulation of neuronal protein expression (Fig.…”

Section: Excitatory Glyr Function and Cellular Signalingmentioning

confidence: 99%

Molecular architecture of glycinergic synapses

Dresbach

Nawrotzki

Kremer

et al. 2008

Histochem Cell Biol

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Synapses can be considered chemical machines, which are optimized for fast and repeated exocytosis of neurotransmitters from presynaptic nerve terminals and the reliable electrical or chemical transduction of neurotransmitter binding to the appropriate receptors in the postsynaptic membrane. Therefore, synapses share a common repertoire of proteins like, e.g., the release machinery and certain cell adhesion molecules. This basic repertoire must be extended in order to generate speciWcity of neurotransmission and allow plastic changes, which are considered the basis of developmental and/or learning processes. Here, we focus on these complementary molecules located in the presynaptic terminal and postsynaptic membrane specializations of glycinergic synapses. Moreover, as speciWcity of neurotransmission in this system is established by the speciWc binding of the neurotransmitter to its receptor, we review the molecular properties of glycine receptor subunits and their assembly into functional glycine receptors with diVerent functional characteristics. The past years have revealed that the molecular machinery underlying inhibitory and especially glycinergic postsynaptic membrane specializations is more complex and dynamic than previously anticipated from morphological studies. The emerging features include structural components as well as signaling modules, which could confer the plasticity required for the proper function of distinct motor and sensory functions.

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GABA sets the tempo for activity-dependent adult neurogenesis

Cited by 328 publications

References 68 publications

Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

Spatial learning sculpts the dendritic arbor of adult-born hippocampal neurons

Compensatory Neurogenesis in the Injured Adult Brain

Molecular architecture of glycinergic synapses

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